The work will attempt to ascertain the metabolic bases for reversible and irreversible neural transmission failure in mammalian brain tissue. Our study focuses on neural transmission in the guinea pig hippocampal slice. We shall further explore the probability that a dcrease in tissue (ATP) is causing transmission failure by studying the effects of small changes in ATP upon neural transmission and comparing this with measured effects of hypoxia. We shall examine the role of increased tissue acidity by producing alterations in intracellular pH and correlating these with alterations in neural function. These effects will then be compared with the effects on intracellular pH which occur during anoxia. In particular, we shall carry out studies to try to distinguish between intracellular pH changes in neuronal and glial elements during anoxia and when intracellular pHi, altered by changing CO2 and HCO3 in the extracellular. In these studies we shall, when necessary, inhibit carbonic anhydrase using bensolamide. Concurrently, we shall begin experiments to determine the metabolic correlates of irreversible electronical damage during anoxia. In our early work we shall study metabolite and pH profiles of tissue at various levels of irreversible damage and endeavor to draw correlations between metabolite and electrical alterations.